Diallyl trisulfide attenuates hyperglycemia-induced endothelial apoptosis by inhibition of Drp1-mediated mitochondrial fission
Diallyl trisulfide attenuates hyperglycemia-induced endothelial apoptosis by inhibition of Drp1-mediated mitochondrial fission
复制标题
二烯丙基三硫化物通过抑制 Drp1 介导的线粒体裂变来减轻高血糖诱导的内皮细胞凋亡
DOI：
10.1007/s00592-019-01366-x
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发表时间：
2019-11-01
影响因子：
3.8
通讯作者：
Huang, Zhen-Hao
中科院分区：
文献类型：
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作者：
Hao, Ying;Liu, Hui-Min;Huang, Zhen-Hao
高血压可诱导内皮细胞凋亡和血管损伤，而二烯丙基三硫化物（DATS）在动物模型和人体中显示出心血管保护作用。本研究旨在探讨DATS对高糖诱导的内皮细胞凋亡的抑制作用及其分子机制。方法人脐静脉内皮细胞（HUVECs）与DATS共同孵育（100 μ M）培养30分钟，然后在高糖培养基中培养（HG，33 mM）24小时，以使用末端脱氧尿苷三磷酸缺口末端标记（TUNEL）、流式细胞术和流式细胞术评估细胞凋亡、谷胱甘肽（GSH）、活性氧物质（ROS）、超氧化物歧化酶（SOD）和基因表达。caspase-3活性、ROS、SOD和蛋白质印迹分析以及JC-1和MitoTracker Red染色。结果DATS通过抑制高糖诱导的HUVEC细胞内和线粒体内活性氧的产生，维持线粒体膜电位，抑制高糖诱导的动力蛋白相关蛋白1（Drp 1）的表达，显著抑制高糖诱导的HUVEC凋亡。此外，DATS阻断高糖诱导的线粒体分裂和凋亡是通过腺苷一磷酸活化蛋白激酶（AMPK）激活抑制HUVECs中Drp 1的表达。结论DATS通过AMPK依赖性抑制Drp 1介导的线粒体分裂，从而抑制高糖诱导的HUVEC凋亡。
Aims Hyperglycemia induces endothelial cell apoptosis and blood vessel damage, while diallyl trisulfide (DATS) has shown cardiovascular protection in animal models and humans. The aim of this study was to investigate the effects of DATS on inhibition of high glucose-induced endothelial cell apoptosis and the underlying molecular events. Methods Human umbilical vein endothelial cells (HUVECs) were incubated with DATS (100 mu M) for 30 min and then cultured in high-glucose medium (HG, 33 mM) for 24 h for assessment of apoptosis, glutathione (GSH), reactive oxygen species (ROS), superoxide dismutase (SOD), and gene expression using the terminal deoxyuridine triphosphate nick end labeling (TUNEL), flow cytometry, caspase-3 activity, ROS, SOD, and western blot assays as well as JC-1 and MitoTracker Red staining, respectively. Results DATS treatment significantly inhibited high glucose-induced HUVEC apoptosis by blockage of intracellular and mitochondrial ROS generation, maintenance of the mitochondrial membrane potential, and suppression of high glucose-induced dynamin-related protein 1 (Drp1) expression. Furthermore, DATS blockage of high glucose-induced mitochondrial fission and apoptosis was through adenosine monophosphate-activated protein kinase (AMPK) activation-inhibited Drp1 expression in HUVECs. Conclusions DATS demonstrated the ability to inhibit high glucose-induced HUVEC apoptosis via suppression of Drp1-mediated mitochondrial fission in an AMPK-dependent fashion.